Mazen Kheirbek, PhD

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Overview

Academic Appointments

Assistant Professor of Clinical Neurobiology in Psychiatry

Research

Our primary interest is dissecting the neuronal circuits that underlie emotional and motivational behavior. To accomplish this, we take an integrative approach, combining genetic, behavioral, electrophysiological and optical techniques to probe and manipulate these circuits in mouse models.

Our research group is focused on understanding the neuronal circuits that underlie emotional behavior, so that we may understand how they go awry in certain anxiety disorders. For this, we have focused on the hippocampus (HPC), which, in addition to its role in learning and memory, has become increasingly implicated in the pathophysiology of anxiety disorders. Recently, using optogenetic techniques, we have shown that the HPC is functionally heterogeneous along its dorsoventral axis, with the dorsal pole playing a role in exploratory behavior and contextual processing and the ventral pole driving anxiety like behaviors. Our current efforts are focused on dissecting the projections of the HPC to limbic regions (amygdala and hypothalamus) in the control of emotional behavior. We compliment these efforts with freely moving, cell-type specific functional imaging techniques to determine a neuronal signature for fear and anxiety within hippocampal circuits. In addition, we are investigating how the hippocampus encodes experiences that have differing emotional valence (for example fearful vs safe or appetitive vs aversive).

In brief, our research is focused on: 1. Functional mapping of the input-output circuitry of the hippocampus in the control of emotional behavior; 2. How emotionally salient information is represented in the hippocampus, and how emotional state (such as increased anxiety) modulates hippocampal function; 3. How early-life development of hippocampal circuitry impacts adult emotional behavior; 4. Determining novel signatures for fear and anxiety within population activity in the hippocampus.

For this we use behavioral, genetic and electrophysiological techniques, cell-type specific functional calcium imaging (freely moving miniaturized microscopes and 2-photon in vivo imaging), and optogenetic/chemogenetic perturbations to probe these circuits that underlie emotional behavior.

Grants

THE ROLE OF NEUROGENESIS IN HIPPOCAMPAL EXCITABILITY AND THE ANTIDEPRESSANT RESPONSE (Private)